The objectives of the proposed research are: a) to synthesize biotrans-formation-resistant phosphoglycerides and related analogs that have pulmonary surfactant activity; b) to compare surfactant and other physico-chemical properties of elaborated phospholipids with those of natural lung surfactant using physical methods and to investigate surfactant structure activity relationships; c) to evaluate activity and clinical potential of pulmonary surfactant phospholipid in the excised lung and in appropriate animal models in vivo; and d) to undertake studies on the formulation of surfactant phospholipid mixtures suitable for introduction into the lung. The main clinical objective is to develop a specific therapy for treatment of Respiratory Distress Syndrome, which is responsible for about 25,000 infant deaths yearly in the United States. Phospholipids of similar and diverse structure, as compared with natural pulmonary surfactant phosphoglycerides, would be prepared by conventional and innovative chemical syntheses. Surface properties of synthetic phospholipids would be determined using a modified Wilhelmy automated recording surface balance. Physiological evaluation of surfactant phospholipids would be carried out in excised lung (rat, dog) and in sheep foeti.